Effects of emotional valence and intensity on cognitive and affective empathy after insula lesions.

The insula plays a central role in empathy. However, the complex structure of cognitive (CE) and affective empathy (AE) deficits following insular damage is not fully understood. In the present study, patients with insular lesions (n = 20) and demographically matched healthy controls (n = 24) viewed ecologically valid videos that varied in terms of valence and emotional intensity. The videos showed a person (target) narrating a personal life event. In CE conditions, subjects continuously rated the affective state of the target, while in AE conditions, they continuously rated their own affect. Mean squared error (MSE) assessed deviations between subject and target ratings. Patients differed from controls only in negative, low-intensity AE, rating their own affective state less negative than the target. This deficit was not related to trait empathy, neuropsychological or clinical parameters, or laterality of lesion. Empathic functions may be widely spared after insular damage in a naturalistic, dynamic setting, potentially due to the intact interpretation of social context by residual networks outside the lesion. The particular role of the insula in AE for negative states may evolve specifically in situations that bear higher uncertainty pointing to a threshold role of the insula in online ratings of AE.

Review and meta-analysis of neuropsychological findings in autoimmune limbic encephalitis with autoantibodies against LGI1, CASPR2, and GAD65 and their response to immunotherapy.

OBJECTIVES: It is assumed that autoimmune limbic encephalitis (ALE) demonstrates distinct neuropsychological manifestations with differential responses to immunotherapy according to which associated autoantibody (AAB), if any, is identified. Towards investigating whether this is the case, this study aims to summarize respective findings from the primary literature on ALE with AABs binding to cell surface neural antigens and ALE with AABs against intracellular neural antigens. METHODS: We chose ALE with AABs against leucine-rich, glioma inactivated protein 1 (LGI1) and contactin-associated protein-like 2 (CASPR2) as the most frequent cell surface membrane antigens, and ALE with AABs to Embryonic Lethal, Abnormal Vision, Like 1 (ELAVL) proteins (anti-Hu) and glutamic acid decarboxylase 65 (GAD65) as the most frequent intracellular neural antigens. The PubMed and Scopus databases were searched on March 1st, 2021 for neuropsychological test and -screening data from patients with ALE of these AAB-types. Findings were reviewed according to AAB-type and immunotherapy status and are presented in a review section and are further statistically evaluated and presented in a meta-analysis section in this publication. RESULTS: Of the 1304 initial hits, 32 studies on ALE with AABs against LGI1, CASPR2, and GAD65 reporting cognitive screening data could be included in a review. In ALE with AABs against LGI1, CASPR2 and GAD65, memory deficits are the most frequently reported deficits. However, deficits in attention and executive functions including working memory, fluency, and psychological function have also been reported. This review shows that ALE patients with AABs against both LGI1 and CASPR2 show higher percentages of neuropsychological deficits compared to ALE patients with AABs against GAD65 before and after initiation of immunotherapy. However, the methodologies used in these studies were heterogenous, and longitudinal studies were not comparable. Moreover, 21 studies including ALE patients with AABs against LGI1 and GAD65 were also suitable for meta-analysis. No suitable study on ALE with AABs against ELAVL proteins could be identified. Meta-Analyses could be executed for cognitive screening data and only partially, due to the small number of studies. However, in statistical analysis no consistent effect of AAB or immunotherapy on performance in cognitive screening tests could be found. CONCLUSION: Currently, there is no definite evidence supporting the notion that different AAB-types of ALE exhibit distinct neuropsychological manifestations and respond differently to immunotherapy. Overall, we could not identify evidence for any effect of immunotherapy on cognition in ALE. More systematic, in-depth and longitudinal neuropsychological assessments of patients with different AAB-types of ALE are required in the future to investigate these aspects.

Lateralized deficits in arousal processing after insula lesions: Behavioral and autonomic evidence.

A large body of evidence ascribes a pivotal role in emotion processing to the insular cortex. However, the complex structure and lateralization of emotional deficits following insular damage are not understood. Here, we investigated emotional ratings of valence and arousal and skin conductance responses (SCR) to a graded series of emotionally arousing scenes in patients with left (n = 10) or right (n = 9) insular damage and in healthy controls (n = 18). We found a significant reduction in overall SCRs, arousal ratings and valence extremity scores in right-lesioned patients, as compared to left-lesioned patients and healthy controls. The degree of right insular damage was significantly correlated with the degree of arousal, SCR and extremity attenuation. Additional analyses of correlations between subjective arousal ratings resp. SCR and normative arousal ratings revealed that both lesion groups had evaluative and physiological difficulties to discover changes in stimulus arousal. Although no group differences emerged on overall ratings of valence, analysis of correlations between subjective and normative valence ratings displayed markedly reduced accuracy in right-lesioned patients, as compared to left-lesioned patients and healthy controls. Our findings support the hypothesis that the left and right insulae subserve different functions in emotion processing, potentially due to asymmetrical representations of autonomic information in the left and right human forebrain. The right insula may serve as integral node for sympathetic arousal and cognitive-affective processing.

Lateralized Deficits of Disgust Processing After Insula-Basal Ganglia Damage.

A growing body of evidence suggests a role of the insular cortex (IC) and the basal ganglia (BG) in the experience, expression, and recognition of disgust. However, human lesion research, probing this structure-function link, has yielded rather disparate findings in single cases of unilateral and bilateral damage to these areas. Comparative group approaches are needed to elucidate whether disgust-related deficits specifically follow damage to the IC-BG system, or whether there might be a differential hemispheric contribution to disgust processing. We examined emotional processing by means of a comprehensive emotional test battery in four patients with left- and four patients with right-hemispheric lesions to the IC-BG system as well as in 19 healthy controls. While single tests did not provide clear-cut separations of patient groups, composite scores indicated selective group effects for disgust. Importantly, left-lesioned patients presented attenuated disgust composites, while right-lesioned patients showed increased disgust composites, as compared to each other and controls. These findings propose a left-hemispheric basis of disgust, potentially due to asymmetrical representations of autonomic information in the human forebrain. The present study provides the first behavioral evidence of hemispheric lateralization of a specific emotion in the human brain, and contributes to neurobiological models of disgust.

Amygdala enlargement and emotional responses in (autoimmune) temporal lobe epilepsy.

Temporal lobe epilepsy with amygdala enlargement (TLE-AE) is increasingly recognized as a distinct adult electroclinical syndrome. However, functional consequences of morphological alterations of the amygdala in TLE-AE are poorly understood. Here, two emotional stimulation designs were employed to investigate subjective emotional rating and skin conductance responses in a sample of treatment-naïve patients with suspected or confirmed autoimmune TLE-AE (n = 12) in comparison to a healthy control group (n = 16). A subgroup of patients completed follow-up measurements after treatment. As compared to healthy controls, patients with suspected or confirmed autoimmune TLE-AE showed markedly attenuated skin conductance responses and arousal ratings, especially pronounced for anxiety-inducing stimuli. The degree of right amygdala enlargement was significantly correlated with the degree of autonomic arousal attenuation. Furthermore, a decline of amygdala enlargement following prompt aggressive immunotherapy in one patient suffering from severe confirmed autoimmune TLE-AE with a very recent clinical onset was accompanied by a significant improvement of autonomic responses. Findings suggest dual impairments of autonomic and cognitive discrimination of stimulus arousal as hallmarks of emotional processing in TLE-AE. Emotional responses might, at least partially, recover after successful treatment, as implied by first single case data.